Aryl thiocyanates, synthesis

In the unconventional synthesis of thioethers (Scheme 4.11), cyanide ion is displaced from thiocyanates by carbanions [52, 53], which have been generated under phase-transfer catalytic conditions (cf. 4.1.12). Thiocyanates are readily obtained by a standard catalysed nucleophilic substitution reaction [4, 54-58] (see Table 4.19). Aryl thiocyanates are obtained from activated aryl halides [4, 57] (see Chapter 2). 

DEPC serves as a coupling agent for the synthesis of simple amides, esters, a-aminonitriles, and aryl thiocyanates it is also used as an efficient coupling agent for racemization-free peptide synthesis. Amides of various types can be obtained by the simple mixing of carboxylic acids and amines with DEPC in the presence of triethylamine. Both aromatic and aliphatic acids easily react with aromatic and aliphatic... 

Hosseini-Sarvari, M. and Tavakohan, M. 2008. Synthesis of aryl thiocyanates using AI2O3/ MeSOjH (AMA) as a novel heterogeneous system. J. Chem. Res. (6) 318-321. 

A full paper detailing the conversion of primary alkylamines into the corresponding thiocyanates has appeared,and this important contribution to thiocyanate synthesis has now been extended to include aromatic derivatives. Thus, the readily prepared (56) reacts, in refluxing ethanol, with arylamines to give (57), which are smoothly pyrolysed to aryl thiocyanates in preparatively useful yields (Scheme 55). 

The combination of alkyl- or aryl-sulphenyl chlorides and trimethylsilyl cyanide in acetonitrile results in complete conversion into the corresponding thiocyanates within one hour at room temperature. This procedure then represents a new synthesis of alkyl or aryl thiocyanates free from isomeric isothiocyanates, from thiols, or from disulphides (Scheme 56). 

Miscellaneous Transformations. Cyanotrimethylsilane effects the transformation of acyl chlorides to acyl cyanides, a-chloro ethers and a-chloro thioethers to a-cyano ethers and a-cyano thioethers (eq 19), t-butyl chlorides to nitriles (eqs 20 and 21), 1,3,5-trisubstituted hexahydro-l,3,5-triazines to amino-acetonitriles, the cyanation of allylic carbonates and acetates (eqs 22 and 23), and the formation of aryl thiocyanates from aryl sulfonyl chlorides and sulfinates. The reagent has been used effectively in peptide synthesis and in a range of other synthetic applications. " ... 

Many nitriles have been used. Even aryl nitriles give good yields if they are first treated with HC1 and ZnCl2 and then the substrate added at 0°C.357 In fact, this procedure increases yields with any nitrile. If thiocyanates RSCN are used, thiol esters ArCOSR can be obtained. The Gatterman reaction (1-16) is a special case of the Hoesch synthesis. 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

The earliest method of this type was the old Marckwald synthesis (1] in which a suitable a-aminocarbonyl compound is cyclized with cyanate, thiocyanate or isothiocyanatc. More recent modifications have employed the acetals of the a-amino aldehyde or ketone or an a-amino acid ester. The two-carbon fragment can also be provided by cyanamide, a thioxamate, a carbodiimidc or an imidic ester. When cyanates, thiocyanates or isothiocyanates are used, the imidazolin-2-ones or -2-thiones (1) are formed initially, but they can be converted into 2-unsubstituted imidazoles quite readily by oxidative or dehydrogenative means (Scheme 4.1.1). The chief limitations of the method arc the difficulty of making some a-aminocarbonyls and the very limited range of 2 substituents which are possible in the eventual imidazole products. The method is nonetheless valuable and widely used, and typically condenses the hydrochloride of an a-amino aldehyde or ketone (or the acetals or ketals), or an a-amino-)6-ketoester with the salt of a cyanic or thiocyanic acid. Usually the aminocarbonyl hydrochloride is warmed in aqueous solution with one equivalent of sodium or potassium cyanate or thiocyanate. An alkyl or aryl isocyanate or isothiocyanate will give an A-substituted imidazole product (2), as will a substituted aminocarbonyl compound (Scheme 4.1.1) [2-4]. 

Aryl sulfones have been prepared from sulfinic acid salts, aryl iodides and Formation of thiocyanates from unactivated aryl halides has been accomplished with charcoal supported copper(l) thiocyanate. " The copper catalyzed reaction of Na02SMe and aryl iodides give the aryl methyl sulfone. " A similar synthesis of diaryl sulfones has been reported using a palladium catalyst. " ... 

Preparation of Thiocyanates.—Variations of standard methods for the synthesis of thiocyanates are illustrated in the addition of alkoxy- and thiocyanato-groups to alkenes using KSCN, CuClj (or other Cu salt), and an alcohol as solvent, to give a-alkoxy-alkyl thiocyanates and in the addition of pseudohalogens CISCN or (SCN)a to chalcones. A sulphonylthiocyanate RSOaSCN, prepared from (SCN)a and a sodium sulphinate, adds similarly to alkenes to give a-thio-cyanato-alkyl sulphones. > Aryl selenocyanates may be prepared from the... 

A very simple, but quite efficient, one-step synthesis of A-aryl-thioureas from primary aromatic amines and ammonium thiocyanate has been reported. Activated isothiocyanates, such as methoxycarbonyl isothiocyanate (1) and acyl or aroyl isothiocyanates, have been applied in the preparation of the JV-heteroaryl-thioureas (2) and (3), or acyl-thioureas (4). Chloroacetyl isothiocyanate... 

Further classes of A -thiazolines have been produced by Hantzsch s synthesis they include 3,4,5-trisubstituted 2-thio-A -thiazolines, 2-aryl-imino-3-aryl-4-methyl-A -thiazolines, 2-arylimino-3-diphenylphosphinyl-amino-A -thiazolines, 3,4-diaryl-2-[(arylsulphonyl)cyanomethylene]-A -thiazolines, and their 2-[(carbonamido)cyanomethylene] analogues. The interaction of phenacyl thiocyanate (163) and arylamines yields 2-imino-3-aryl-4-phenyl-A -thiazolines (165). The parallel intramolecular cyclization of (163) to 2-hydroxy-4-phenylthiazole (164) is not significant... 

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